Transfection, a process for delivering an exogenous specific gene into cells, is an indispensable way for obtaining useful information for the treatment of diseases and the development of medicines, by analyzing the action mechanism in which the gene is involved. In such transfection, trials have been recently made to use non-viral effects in order to avoid harmful effects upon the organism. It has been pointed out that there are big barriers to the improvement of transfection efficiency with a non-viral vector, including the passage through the cytomembrane, the escape from transport vesicles, the nuclear import, and the DNA release of a nucleic acid until the nucleic acid is lead to the transcription reaction.    Non-patent reference 1: MarShall, E. (1999) Science 286, 2244-2245.    Non-patent reference 2: Hacein-Bey-Abina, S., Von Kalle, C., Schmidt, M., McCormack, M. P., Wulffrat, N., Leboulch, P., Lim, A., Osborne, C, S., Pawliuk, R., Morillion, E., Sorensen, R., Forster, A., Fraser, P., Cohen, J. I., de Saint Basile, G., Alexander, I., W intergerst, U., Frebourg., T., Aurias, A. D., Stoppa-Lyonnet, D., Romana, S., Radford-Weiss, I., Gross, F., Valensi, F., Delabesse, E., Macintyre, E., Sigaux, F., Soulier, J., Leiva, L. E., Wissler, M., Prinz, C., Rabbitts, J., Le Deist, F., Fischer, A., and Cavazzana-Calvo M. (2003) Science 302, 415-419.    Non-patent reference 3: Huang, L., Hung, M.-C., and Wagner E. (1999) Nonviral Vectors for Gene Therapy, AcademicPress, San Diego.    Non-patent reference 4: Rolland, A (1999) Advanced Gene Delivery, Harwood Academic Publishers, Amsterdam.    Non-patent reference 5: Wiethoff, C. M., and Middaugh, C. R. (2003) J. Pharm. Sci., 92, 203-217.
As a way to improve the cytomembrane passage, utilization of cell membrane receptor-binding factors has been studied, and an improvement is seen via the receptor-mediated endocytosis.    Non-patent reference 6: Vyas S P, Singh A. Sihorkar V. (2001) Crit Rev Ther Drug Carrier Syst., 18(1), 1-76.
Most of non-viral vectors can pass through the cell membrane via endocytosis, but, if they are left as they are, decompose resulting in a low expression efficiency. Thus, as a measure to improve the escape from transport vesicles, studies have been conducted on the utilization of pH-sensitive membrane-fusing substances, with recognized effectiveness.    Non-patent reference 7: Cho, Y. W., Kim, J. D., and Park, K. (2003) J. Pharm Pharmacol., 55 (6), 721-34.
The nuclear import of exogenous genes can be counted as one of the biggest barriers to the improvement of transfection efficiency in the use of non-viral vectors. As an approach for overcoming this issue, extensive studies have been made on the utilization of the nuclear import system of nuclear proteins in eukaryotic cells.
Nuclear proteins are generally tagged with a nuclear localization signal (NLS), to which is bound importin-α, a mediator for the material to be imported. There is finally formed a complex in which importin-β is bound to the importing material, for energy-dependent and selective import of nucleic acid through the nuclear pores present in the nuclear envelope.    Non-patent reference 9: Pexach, M., and Blobel, G., Cell 83, 683-692, (1995).    Non-patent reference 10: Yoneda, Y., J. Biochem, Tokyo 121, 811-817 (1996).
Thus, a number of studies have been made on the promotion of nuclear import and, by extension, the enhancement of expression efficiency, by complexing exogenous gene with a NLS peptide. However, the methodology has not yet been established since advantageous effects are ascertained in some cases, whereas there are some reports negating significant effects on expression efficiency. This may be partly because the formation of the complex proceeds in two-staged reactions resulting in a decreased efficiency.    Non-patent reference 11: Zanta, M. A., Belguise-Valladier, P., and Behr, J. P., Proc. Natl. Acad. Sci. U.S.A. 96 91-96 (1999).    Non-patent reference 12: Collas, P., and Alestrom, P., Biochem. Cell. Biol., 75, 6333-640(1997).    Patent reference 1: Japanese Patent Application Publication No. 1999-506935.    Patent reference 2: Japanese Patent Application Publication No. 2002-514892.    Patent reference 3: Japanese Patent Application Publication No. 2002-533088.    Non-patent reference 13: Nagasaki, T., Myohoji, T., Tachibana, T., and Tamagaki., S., Bioconjugate Chem., 14, 282-286 (2003).    Non-patent reference 14: Tanimoto, M., Kamiya, H., Minakawa, N., Matsuda, A and Harashuma, H., Bioconjugate Chem., 14, 1197-1202 (2003).
It is further to be noted that the expression efficiency is lowered when the exogenous gene is imported into the nucleus as it is bound with the carrier compound which functions as a non-viral vector. Therefore studies have been made on stimuli-responsive carriers, such as photo-responsive or redox-responsive carriers, for the enhancement of DNA release in the nucleus.    Non-patent reference 15: Miyata, K., Kakizawa, Y., Nishiyama, N., Harada, A., Yamazaki, Y., Koyama, H., Kataoka, K (2004) J Am Chem Soc., 126 (8), 2355-61.
Thus, although means have been proposed, on a piecemeal basis, for overcoming the barriers to non-viral vectors in the transport process of a nucleic acid from outside of a cell into the cell nucleus, there are found no organized systems providing collective advantageous effects by the non-viral vectors with a satisfactory efficiency.